This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The optimal criteria for switching therapy have yet to be defined. There is a logical argument in favor of strict control of the viral replication. Consequently, this control dictates that as soon as virus becomes detectable in the circulation (or if plasma viral load fails to reach undetectable limits), then a switch should be made to a different and probably more intensive regimen. The problem with this approach, given the limitations of drugs available to children, is that this policy may rapidly exhaust all available options for therapy. An alternative approach, which may be equally valid over a long period of followup, would be to try to maximize the benefit of each regimen and switch only when the viral load is consistently above a higher threshold. This strategy will preserve options longer, and there is some evidence that virus replicating despite HAART may be less pathogenic in-vivo.